Medical device with controlled reservoir opening

• US 7,918,842 B2
• Filed: 02/20/2004
• Issued: 04/05/2011
• Est. Priority Date: 07/02/1996
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Santini, John T. Jr., Cima, Michael J., Langer, Robert S.
• Primary Examiner(s): Lucchesi; Nicholas D
• Assistant Examiner(s): VU, QUYNH-NHU HOANG
• Application Number:
  US10/783,897
• Publication Number:
  US 20040166140A1
• Time in Patent Office: 2,601 Days
• Field of Search: 604/890.1, 604/891.1, 604/892.1, 604/19, 604/93.01, 604/20, 604/500, 604/501, 128/899, 137/67
• US Class Current: 604/890.1
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: C25F 5/00 Electrolytic stripping of metallic layers or coatings
• CPC Class Codes: C25F 7/00 Constructional parts, or assemblies thereof, of cells for electrolytic removal of material from objects for both electrolytic coating and removal C25D; Servicing or operating
• CPC Class Codes: Y10T 137/8242 Electrical

Abstract

Implantable medical devices are provided for controlled release of drugs. In one embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo disintegration of the matrix material. In another embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a non-degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo diffusion of the drug molecules from the matrix material.

Claims

1. An implantable medical device for the controlled release of drug molecules comprising:

a substrate;

at least two reservoirs in the substrate;

release system disposed in the reservoirs, the release system comprising drug molecules for release; and

discrete metal reservoir caps positioned over or within openings in the reservoirs, wherein release of the drug molecules from the device is activated by disintegration of the reservoir cap and the disintegration of the reservoir cap is actively controlled.

2. The device of claim 1, wherein the substrate is comprised of two or more substrate portions bonded together.

3. The device of claim 2, wherein the substrate comprises an upper substrate portion adjacent the reservoir cap and a lower substrate portion distal the reservoir cap.

4. The device of claim 3, wherein a reservoir section in the upper substrate portion is in communication with a reservoir section in the lower substrate portion, the two reservoir sections forming a single reservoir.

5. The device of claim 3, wherein the reservoir section in the lower substrate portion has a volume that is greater than the volume of the reservoir section in the upper substrate portion.

6. The device of claim 3, wherein the lower substrate portion is provided with an internal reservoir cap interposed between a reservoir section of the upper substrate portion and a reservoir section of the lower substrate portion, wherein release of the molecules from the reservoir section in the lower substrate portion is controlled by diffusion through or disintegration of the internal reservoir cap.

7. The device of claim 6, wherein the internal reservoir cap is disintegratable, so that the two reservoir sections become a single reservoir upon disintegration of the internal reservoir cap.

8. The device of claim 6, wherein the reservoir section of the lower substrate portion contains molecules different in quantity, type, or both quantity and type, from the molecules contained in the reservoir section of the upper substrate portion.

9. The device of claim 1, wherein disintegration of the reservoir cap is activated by application of electrical energy through the reservoir cap.

10. The device of claim 9, wherein at least one reservoir cap is an anode, and the device further comprises a cathode, a power source, and electrical circuitry means for application of an electric potential between the cathode and anode effective to disintegrate the reservoir cap.

11. The device of claim 1, wherein the release system further comprises at least one matrix material, excipient, or combination thereof.

12. The device of claim 1, wherein the release system further comprises at least one biodegradable or bioerodible polymeric material.

13. The device of claim 1, wherein the drug molecules comprise anesthetics, vaccines, chemotherapeutic agents, metabotites, immunomodutators, antioxidants, antibiotics, and ion channel regulators, or hormones.

14. The device of claim 1, wherein the disintegration of at least one of the reservoir caps is controlled by a signal from a biosensor or by a preprogrammed microprocessor.

15. A microchip device for the controlled release of drug molecules comprising:

a substrate;

at least two reservoirs in the substrate, wherein each reservoir has at least one opening defined in the substrate;

release system disposed in the reservoirs, the release system comprising drug molecules for release; and

at least two discrete electrically conductive reservoir caps, each reservoir cap closing off the opening defined by a respective reservoir,

wherein release of the drug molecules from the device is activated by disintegration of the reservoir cap by direct application of an electrical potential through the reservoir cap.

16. The device of claim 15, wherein the substrate is comprised of two or more substrate portions bonded together.

17. The device of claim 16, wherein the drug molecules comprise anesthetics, vaccines, chemotherapeutic agents, metabolites, immunomodulators, antioxidants, antibiotics, and ion channel regulators, or hormones.

18. The device of claim 15, wherein at least one reservoir cap is an anode, and the device further comprises a cathode, a power source, and electrical circuitry means for application of an electric potential between the cathode and anode effective to disintegrate the reservoir cap.

19. The device of claim 15, wherein the release system in at least one of the reservoirs differs in quantity, type, or both quantity and type, from the release system in at least one other of the reservoirs.

20. The device of claim 15, wherein the release system further comprises at least one matrix material, excipient, or combination thereof.

21. The device of claim 15, wherein the release system further comprises at least one biodegradable or bioerodible polymeric material.

22. The device of claim 15, wherein the reservoir caps are formed of a metal film.

23. A medical device comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions across at least one surface of the substrate;

discrete reservoir caps covering the at least two reservoirs; and

control circuitry for selectively disintegrating the reservoir caps to open the reservoirs;

wherein the reservoir caps comprise a metal film.

24. A device for use in medical diagnostics comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions across at least one surface of the substrate;

a diagnostic reagent disposed in the reservoirs;

discrete reservoir caps covering the at least two reservoirs; and

control circuitry for selectively disintegrating the reservoir caps to open the reservoirs;

wherein the reservoir caps comprise a metal film.

25. A medical device comprising:

a substrate;

at least two discrete reservoirs provided in spaced positions across at least one surface of the substrate;

discrete reservoir caps covering the at least two reservoirs; and

control circuitry for selectively disintegrating the reservoir caps to open the reservoirs,

wherein the reservoir cap disintegration comprises dissolving into solution, or forming soluble ions or oxidation compounds, upon application of an electric potential generated by the control circuitry.

26. The medical device of claim 25, wherein the control circuitry comprises a cathode and a power source, wherein at least one reservoir cap is an anode, and wherein application of an electric potential between the cathode and anode causes at least one of the reservoir caps to disintegrate.

27. The device of claim 25, wherein the reservoirs comprise molecules useful in medical diagnostics.

28. The device of claim 27, wherein the molecules comprise a diagnostic reagent.

29. The device of claim 25, wherein the reservoirs comprise drug molecules.

30. The device of claim 25, wherein the reservoirs are microfabricated, at least one of the reservoirs contains drug or diagnostic molecules, and the device is adapted for implantation into a patient.